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1.
Mol Genet Genomic Med ; 12(7): e2494, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39056574

ABSTRACT

BACKGROUND: We clinically and genetically evaluated a Taiwanese boy presenting with developmental delay, organomegaly, hypogammaglobulinemia and hypopigmentation without osteopetrosis. Whole-exome sequencing revealed a de novo gain-of-function variant, p.Tyr715Cys, in the C-terminal domain of ClC-7 encoded by CLCN7. METHODS: Nicoli et al. (2019) assessed the functional impact of p.Tyr715Cys by heterologous expression in Xenopus oocytes and evaluating resulting currents. RESULTS: The variant led to increased outward currents, indicating it underlies the patient's phenotype of lysosomal hyperacidity, storage defects and vacuolization. This demonstrates the crucial physiological role of ClC-7 antiporter activity in maintaining appropriate lysosomal pH. CONCLUSION: Elucidating mechanisms by which CLCN7 variants lead to lysosomal dysfunction will advance understanding of genotype-phenotype correlations. Identifying modifier genes and compensatory pathways may reveal therapeutic targets. Ongoing functional characterization of variants along with longitudinal clinical evaluations will continue advancing knowledge of ClC-7's critical roles and disease mechanisms resulting from its dysfunction. Expanded cohort studies are warranted to delineate the full spectrum of associated phenotypes.


Subject(s)
Chloride Channels , Humans , Male , Chloride Channels/genetics , Chloride Channels/metabolism , Gain of Function Mutation , Osteopetrosis/genetics , Osteopetrosis/pathology , Phenotype , Child, Preschool
3.
PLoS One ; 19(7): e0307181, 2024.
Article in English | MEDLINE | ID: mdl-39046973

ABSTRACT

Metabolic-associated fatty liver disease (MAFLD) is predominantly associated with metabolic disturbances representing aberrant liver function and increased uric acid (UA) levels. Growing evidences have suggested a close relationship between metabolic disturbances and the gut microbiota. A placebo-controlled, double-blinded, randomized clinical trial was therefore conducted to explore the impacts of daily supplements with various combinations of the probiotics, Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 with a focus on liver function and serum UA levels. Test subjects with abnormal levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and UA were recruited and randomly allocated into six groups. Eighty-two participants successfully completed the 60-day intervention without any dropouts or occurrence of adverse events. The serum AST, ALT, and UA levels were significantly reduced in all treatment groups (P < 0.05). The fecal microbiota analysis revealed the intervention led to an increase in the population of commensal bacteria and a decrease in pathobiont bacteria, especially Bilophila wadsworthia. The in vitro study indicated the probiotic treatments reduced lipid accumulation and inflammatory factor expressions in HepG2 cells, and also promoted UA excretion in Caco-2 cells. The supplementation of multi-strain probiotics (TSF331, TSR332, and TSP05) together can improve liver function and UA management and may have good potential in treating asymptomatic MAFLD. Trial registration. The trial was registered in the US Library of Medicine (clinicaltrials.gov) with the number NCT06183801 on December 28, 2023.


Subject(s)
Lactobacillus plantarum , Limosilactobacillus fermentum , Limosilactobacillus reuteri , Probiotics , Uric Acid , Humans , Probiotics/administration & dosage , Lactobacillus plantarum/physiology , Male , Uric Acid/blood , Uric Acid/metabolism , Female , Pilot Projects , Middle Aged , Double-Blind Method , Liver/metabolism , Adult , Gastrointestinal Microbiome/drug effects , Hep G2 Cells , Caco-2 Cells , Aspartate Aminotransferases/blood , Feces/microbiology , Alanine Transaminase/blood
4.
Front Microbiol ; 15: 1424330, 2024.
Article in English | MEDLINE | ID: mdl-38989021

ABSTRACT

The transcription factor PsrA regulates fatty acid metabolism, the type III secretion system, and quinolone signaling quorum sensing system in Pseudomonas aeruginosa. To explore additional roles of PsrA in P. aeruginosa, this study engineered a P. aeruginosa PAO1 strain to carry a recombinant plasmid with the psrA gene (pMMBpsrA) and examined the impact of elevated psrA expression to the bacterium. Transcriptomic analysis revealed that PsrA significantly downregulated genes encoding the master quorum-sensing regulators, RhlR and LasR, and influenced many quorum-sensing-associated genes. The role of PsrA in quorum sensing was further corroborated by testing autoinducer synthesis in PAO1 [pMMBpsrA] using two reporter bacteria strains Chromobacterium violaceum CV026 and Escherichia coli [pSB1075], which respond to short- and long-chain acyl homoserine lactones, respectively. Phenotypic comparisons of isogenic ΔpsrA, ΔlasR, and ΔpsrAΔlasR mutants revealed that the reduced elastase, caseinase, and swarming activity in PAO1 [pMMBpsrA] were likely mediated through LasR. Additionally, electrophoretic mobility shift assays demonstrated that recombinant PsrA could bind to the lasR promoter at a 5'-AAACGTTTGCTT-3' sequence, which displays moderate similarity to the previously reported consensus PsrA binding motif. Furthermore, the PsrA effector molecule oleic acid inhibited PsrA binding to the lasR promoter and restored several quorum sensing-related phenotypes to wild-type levels. These findings suggest that PsrA regulates certain quorum-sensing phenotypes by negatively regulating lasR expression, with oleic acid acting as a crucial signaling molecule.

5.
Taiwan J Obstet Gynecol ; 63(4): 532-535, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39004481

ABSTRACT

OBJECTIVE: To assess the treatment efficacy of dienogest specifically in the Taiwanese population with endometriosis. MATERIALS AND METHODS: Eighty-eight patients diagnosed with endometriosis receiving at least 3 months of dienogest 2 mg once daily, from January 2018 to June 2022, were enrolled. They were divided into two groups: surgery group and non-surgery group. The assessment of pain improvement was based on visual analog scale (VAS) scores (0-100 mm) recorded at 0, 3, 6, and 12 months following the initiation of dienogest. Serum CA-125 value and ovarian endometrioma size were analyzed at 0 and 6 months. RESULTS: A total of 65 patients with endometriosis presented painful symptoms. In the surgery group (N = 28), the initial VAS score was 47.5 mm, which significantly declined to 9.6 mm at 3 months (p < 0.01), then to 7.5 mm, 2.9 mm, and 2.1 mm at 6, 9, and 12 months, respectively. In the non-surgery group (N = 37), the initial VAS score was 65.7 mm, which significantly declined to 13.2 mm at 3 months (p < 0.01) and 4.9 mm at 6 months (p < 0.05), remained low at 0.3 mm at both 9 and 12 months. Endometrioma size (N = 33) exhibited a significant 35% decrease from 38.2 mm to 24.8 mm after 6 months treatment (p < 0.01). Serum CA-125 levels showed significant improvement from 86.5 to 30.2 U/ml (p < 0.01) at 6 months. CONCLUSION: This retrospective cohort study proved that dienogest is effective in reducing endometriosis-associated pain and endometrioma size in Taiwanese population.


Subject(s)
Endometriosis , Nandrolone , Humans , Female , Endometriosis/drug therapy , Endometriosis/complications , Nandrolone/analogs & derivatives , Nandrolone/therapeutic use , Adult , Taiwan , Retrospective Studies , Treatment Outcome , CA-125 Antigen/blood , Pelvic Pain/drug therapy , Pelvic Pain/etiology , Pain Measurement , Hormone Antagonists/therapeutic use
6.
J Gerontol Soc Work ; : 1-16, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38922327

ABSTRACT

The present survey research investigated older people's volunteering competency relating to social inequality by exploring the latent ability profile and demographic correlates of 1,000 older volunteers in 73 community care centersin southern Taiwan. Older volunteers were classified into advanced (n = 509), basic (n = 214), and novice (n = 277) groups. Demographics examined included: individualistic characteristics (religious beliefs), resources (education; number of chronic diseases), andsocial factors (serving area and spoken language, volunteering duration, marital status, and gender). Apparent inequality issues were revealed. The advanced group was better educated, Mandarin-speaking, and in urban areas. while the novice group featured the opposite (lower education Taiwanese-speaking suburban areas).

7.
Nutrients ; 16(12)2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38931275

ABSTRACT

Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO2max), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion (p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage (p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 (p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.


Subject(s)
Gastrointestinal Microbiome , Lactobacillus plantarum , Lactococcus lactis , Muscle Strength , Physical Endurance , Probiotics , Humans , Probiotics/administration & dosage , Double-Blind Method , Male , Physical Endurance/physiology , Female , Adult , Young Adult , Oxygen Consumption , Muscle, Skeletal/physiology , Exercise/physiology
9.
Int J Mol Sci ; 25(11)2024 May 21.
Article in English | MEDLINE | ID: mdl-38891764

ABSTRACT

Glaucoma is a chronic neurodegenerative disease that poses a significant threat of irreversible blindness worldwide. Current treatments for glaucoma focus on reducing intraocular pressure (IOP), which is the only modifiable risk factor. Traditional anti-glaucomatous agents, including carbonic anhydrase inhibitors, beta-blockers, alpha-2 agonists, and prostaglandin analogs, work by either improving uveoscleral outflow or reducing aqueous humor production. Rho kinase (ROCK) inhibitors represent a novel class of anti-glaucomatous drugs that have emerged from bench to bedside in the past decade, offering multifunctional characteristics. Unlike conventional medications, ROCK inhibitors directly target the trabecular meshwork outflow pathway. This review aims to discuss the mechanism of ROCK inhibitors in reducing IOP, providing neuroprotection, and preventing fibrosis. We also highlight recent studies and clinical trials evaluating the efficacy and safety of ROCK inhibitors, compare them with other clinical anti-glaucomatous medications, and outline future prospects for ROCK inhibitors in glaucoma treatment.


Subject(s)
Glaucoma , Intraocular Pressure , Protein Kinase Inhibitors , rho-Associated Kinases , Humans , Glaucoma/drug therapy , rho-Associated Kinases/antagonists & inhibitors , rho-Associated Kinases/metabolism , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacology , Intraocular Pressure/drug effects , Animals
10.
J Clin Med ; 13(12)2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38930036

ABSTRACT

Objectives: Gait speed indicates the individual's functional status and predicts overall health. This study aims to determine (1) the intra- and inter-rater and test-retest reliability of the dynamic 4 m gait speed test protocol; (2) establish the normative reference values of habitual and fast gait speeds in community-dwelling healthy Singaporean adults aged 21 to 80; and (3) explore the association of age, gender, height, weight, and body mass index (BMI) on gait speed. Methods: This prospective cross-sectional study recruited healthy ambulatory community-dwelling Singaporeans aged 21 to 80 who could ambulate independently without aid. Participants were excluded if they required walking aids; were pregnant; or had physical, medical, or cognitive conditions that may affect gait. Each participant completed at least two habitual and fast gait speed test trials via a 4 m walkway with a dynamic start. The data were analysed by descriptive statistics, the Mann-Whitney test, the Spearman coefficient, and the interclass correlation coefficient (ICC). Results: In total, 178 males and 201 females were included in the data analysis. The median age was 45.0 years [interquartile range (IQR) 26.2-59.0], and the median height was 1.64 metres (m) (IQR 1.58-1.70). The median habitual gait speed was 1.08 metre/second (m/s) (IQR 0.97-1.22), and the fast gait speed was 1.55 m/s (IQR 1.40-1.70). The ICC for reliability ranged from 0.84 to 0.99, indicating that the 4 m gait speed test had good-to-excellent reliability. Conclusions: Gait speeds were not influenced by gender but declined with age advancement. Age and height and age and BMI were weakly correlated to habitual and fast gait speed, respectively. We established the norm values for the 4 m gait speeds in Singapore and proved it to be a reliable gait speed assessment ready for immediate community applications.

11.
Membranes (Basel) ; 14(5)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38786933

ABSTRACT

Three widths of manufacturing S-ribs carbon-fiber filaments acting as turbulence promoters were implemented into the flow channel of direct contact membrane distillation (DCMD) modules to augment the permeate flux improvement in the present study. Attempts to reduce the disadvantageous temperature polarization effect were made by inserting S-ribs turbulence promoters in improving pure water productivity, in which both heat- and mass-transfer boundary layers were diminished due to creating vortices in the flow pattern and increasing turbulence intensity. The temperature polarization coefficient ttemp was studied and found to enhance device performance (less thermal resistance) under inserting various S-ribs carbon-fiber thicknesses and operating both cocurrent- and countercurrent-flow patterns. The permeate fluxes in the DCMD modules with inserted S-ribs carbon-fiber turbulence promoters were investigated theoretically by developing the mathematical modeling equations and were conducted experimentally with various design and operating parameters. The theoretical predictions and experimental results exhibited a great potential to considerably achieve permeate flux enhancement in the new design of the DCMD system. The DCMD module with inserted S-ribs carbon-fiber turbulence promoters in the flow channel could provide a relative permeate flux enhancement up to 37.77% under countercurrent-flow operations in comparisons with the module of using the empty channel. An economic consideration on both permeate flux enhancement and power consumption increment for the module with inserted S-ribs carbon-fiber filaments was also delineated.

12.
Biomed Pharmacother ; 175: 116660, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38701563

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) has an extremely devastating nature with poor prognosis and increasing incidence, making it a formidable challenge in the global fight against cancer-related mortality. In this innovative preclinical investigation, the VCP/p97 inhibitor CB-5083 (CB), miR-142, a PD-L1 inhibitor, and immunoadjuvant resiquimod (R848; R) were synergistically encapsulated in solid lipid nanoparticles (SLNs). These SLNs demonstrated features of peptides targeting PD-L1, EGFR, and the endoplasmic reticulum, enclosed in a pH-responsive polyglutamic (PGA)-polyethylene glycol (PEG) shell. The homogeneous size and zeta potential of the nanoparticles were stable for 28 days at 4°C. The study substantiated the concurrent modulation of key pathways by the CB, miR, and R-loaded nanoformulation, prominently affecting VCP/Bip/ATF6, PD-L1/TGF-ß/IL-4, -8, -10, and TNF-α/IFN-γ/IL-1, -12/GM-CSF/CCL4 pathways. This adaptable nanoformulation induced durable antitumor immune responses and inhibited Panc-02 tumor growth by enhancing T cell infiltration, dendritic cell maturation, and suppressing Tregs and TAMs in mice bearing Panc-02 tumors. Furthermore, tissue distribution studies, biochemical assays, and histological examinations highlighted enhanced safety with PGA and peptide-modified nanoformulations for CB, miR, and/or R in Panc-02-bearing mice. This versatile nanoformulation allows tailored adjustment of the tumor microenvironment, thereby optimizing the localized delivery of combined therapy. These compelling findings advocate the potential development of a pH-sensitive, three-in-one PGA-PEG nanoformulation that combines a VCP inhibitor, a PD-L1 inhibitor, and an immunoadjuvant for cancer treatment via combinatorial chemo-immunotherapy.


Subject(s)
Immunotherapy , Nanoparticles , Pancreatic Neoplasms , Tumor Microenvironment , Animals , Tumor Microenvironment/drug effects , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/pathology , Humans , Immunotherapy/methods , Mice , Cell Line, Tumor , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/immunology , Carcinoma, Pancreatic Ductal/pathology , B7-H1 Antigen/antagonists & inhibitors , Nanoparticle Drug Delivery System/chemistry , Female , Polyethylene Glycols/chemistry , Immune Checkpoint Inhibitors/pharmacology , Liposomes
13.
Nat Commun ; 15(1): 3149, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38605037

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Mice , Animals , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/pathology , Metalloendopeptidases/genetics , Metalloendopeptidases/metabolism
14.
Front Pharmacol ; 15: 1347882, 2024.
Article in English | MEDLINE | ID: mdl-38584602

ABSTRACT

Objective: Our study provides an innovative approach to exploring herbal formulas that contribute to the promotion of sustainability and biodiversity conservation. We employ data mining, integrating keyword extraction, association rules, and LSTM-based generative models to analyze classical Traditional Chinese Medicine (TCM) texts. We systematically decode classical Chinese medical literature, conduct statistical analyses, and link these historical texts with modern pharmacogenomic references to explore potential alternatives. Methods: We present a novel iterative keyword extraction approach for discerning diverse herbs in historical TCM texts from the Pu-Ji Fang copies. Utilizing association rules, we uncover previously unexplored herb pairs. To bridge classical TCM herbal pairs with modern genetic relationships, we conduct gene-herb searches in PubMed and statistically validate this genetic literature as supporting evidence. We have expanded on the present work by developing a generative language model for suggesting innovative TCM formulations based on textual herb combinations. Results: We collected associations with 7,664 PubMed cross-search entries for gene-herb and 934 for Shenqifuzheng Injection as a positive control. We analyzed 16,384 keyword combinations from Pu-Ji Fang's 426 volumes, employing statistical methods to probe gene-herb associations, focusing on examining differences among the target genes and Pu-Ji Fang herbs. Conclusion: Analyzing Pu-Ji Fang reveals a historical focus on flavor over medicinal aspects in TCM. We extend our work on developing a generative model from classical textual keywords to rapidly produces novel herbal compositions or TCM formulations. This integrated approach enhances our comprehension of TCM by merging ancient text analysis, modern genetic research, and generative modeling.

15.
EBioMedicine ; 102: 105047, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38471396

ABSTRACT

BACKGROUND: It has been shown that AI models can learn race on medical images, leading to algorithmic bias. Our aim in this study was to enhance the fairness of medical image models by eliminating bias related to race, age, and sex. We hypothesise models may be learning demographics via shortcut learning and combat this using image augmentation. METHODS: This study included 44,953 patients who identified as Asian, Black, or White (mean age, 60.68 years ±18.21; 23,499 women) for a total of 194,359 chest X-rays (CXRs) from MIMIC-CXR database. The included CheXpert images comprised 45,095 patients (mean age 63.10 years ±18.14; 20,437 women) for a total of 134,300 CXRs were used for external validation. We also collected 1195 3D brain magnetic resonance imaging (MRI) data from the ADNI database, which included 273 participants with an average age of 76.97 years ±14.22, and 142 females. DL models were trained on either non-augmented or augmented images and assessed using disparity metrics. The features learned by the models were analysed using task transfer experiments and model visualisation techniques. FINDINGS: In the detection of radiological findings, training a model using augmented CXR images was shown to reduce disparities in error rate among racial groups (-5.45%), age groups (-13.94%), and sex (-22.22%). For AD detection, the model trained with augmented MRI images was shown 53.11% and 31.01% reduction of disparities in error rate among age and sex groups, respectively. Image augmentation led to a reduction in the model's ability to identify demographic attributes and resulted in the model trained for clinical purposes incorporating fewer demographic features. INTERPRETATION: The model trained using the augmented images was less likely to be influenced by demographic information in detecting image labels. These results demonstrate that the proposed augmentation scheme could enhance the fairness of interpretations by DL models when dealing with data from patients with different demographic backgrounds. FUNDING: National Science and Technology Council (Taiwan), National Institutes of Health.


Subject(s)
Benchmarking , Learning , Aged , Female , Humans , Middle Aged , Black People , Brain , Demography , United States , Asian People , White People , Male , Black or African American
16.
Laryngoscope ; 134(7): 3260-3266, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38501339

ABSTRACT

OBJECTIVES: A small number of Idiopathic subglottic stenosis (iSGS) patients are treated at institutions across the country. Divergence in operative techniques for endoscopic dilation (ED) of iSGS has been anecdotally recognized but not formally characterized. Additionally, the relationship between procedural variation and clinical outcome has not been studied. METHODS: Secondary analysis of the NoAAC iSGS1000 cohort investigated variation in procedural techniques and treatment outcomes in patients treated with ED across high-enrolling treatment centers (enrolled >10 patients in PR-02 trial). RESULTS: Thirteen NoAAC centers each enrolled >10 patients treated with ED for a total of 281 subjects. There was significant variation in procedural details and rate of recurrence among institutions. Hierarchal cluster analysis revealed significant heterogeneity among institutions and clusters in all procedural variables. However, analysis demonstrated a transient delay in disease recurrence in cluster 2 which disappeared with longer longitudinal follow-up. Patient-reported outcome and peak expiratory flow data supported the potential benefit of the technical variation in Cluster 2. Distinct to cluster 2, however, was routine use of adjuvant triple medical therapy (proton pump inhibitor (PPI), antibacterial agent, and steroid inhaler). CONCLUSIONS: Both outcome and procedural technique vary among centers employing ED to treat iSGS. A transient delay in recurrence was observed among centers that routinely prescribed adjuvant medical therapy (antibiotic, inhaled corticosteroid, and PPI) to iSGS patients after endoscopic dilation, which was further supported by patient-reported data and peak expiratory flow data. Prospective studies are needed to understand the effects of adjuvant medical therapy on recurrence after endoscopic dilation. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3260-3266, 2024.


Subject(s)
Dilatation , Laryngostenosis , Humans , Laryngostenosis/surgery , Laryngostenosis/therapy , Dilatation/methods , Male , Female , Middle Aged , Treatment Outcome , Laryngoscopy/methods , Adult , Recurrence , Aged
17.
Curr Issues Mol Biol ; 46(3): 2701-2712, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38534786

ABSTRACT

Inflammation and collagen-degrading enzymes' overexpression promote collagen decomposition, which affects the structural integrity of the extracellular matrix. The polysaccharide and peptide extracts of the green alga Caulerpa microphysa (C. microphysa) have been proven to have anti-inflammatory, wound healing, and antioxidant effects in vivo and in vitro. However, the biological properties of the non-water-soluble components of C. microphysa are still unknown. In the present study, we demonstrated the higher effective anti-inflammatory functions of C. microphysa ethyl acetate (EA) extract than water extract up to 16-30% in LPS-induced HaCaT cells, including reducing the production of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α (TNF-α). Furthermore, the excellent collagen homeostasis effects from C. microphysa were proven by suppressing the matrix metalloproteinase-1 (MMP-1) secretion, enhancing type 1 procollagen and collagen expressions dose-dependently in WS1 cells. Moreover, using UHPLC-QTOF-MS analysis, four terpenoids, siphonaxanthin, caulerpenyne, caulerpal A, and caulerpal B, were identified and may be involved in the superior collagen homeostasis and anti-inflammatory effects of the C. microphysa EA extract.

18.
World J Oncol ; 15(2): 287-297, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38545474

ABSTRACT

Background: The prognosis of upper tract urothelial carcinoma (UTUC) varies, with T3/T4 UTUC having less than 50% 5-year survival post-radical nephroureterectomy (RNU). Lipid profiles including cholesterol (CHOL), low-density lipoprotein (LDL), and triglycerides (TGs), and high-density lipoprotein (HDL) have shown correlations with oncologic outcomes in various cancers. We aimed to investigate the prognostic significance of the lipid profiles in UTUC patients who had received RNU. Methods: In this retrospective study, a total of 217 UTUC patients who underwent RNU were analyzed. Prognostic factors for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression model and competing risk analysis. Results: The median follow-up duration was 2.36 years. Fifty-one (23.50%) of the patients experienced tumor progression, 16 (7.37%) died from UTUC, and 41 (18.89%) died from all causes during the follow-up period. Multivariate analysis revealed that elevated CHOL, low HDL, and elevated TG were linked to worse OS (P = 0.0188, 0.0002, and 0.0001, respectively). Higher CHOL, LDL, and TG, as well as lower HDL significantly affected PFS (P < 0.001 for all), and elevated CHOL and TG were associated with poorer CSS (P = 0.0033 and 0.0179). A competing risk model indicated that elevated LDL increased the risk of cancer progression (P = 0.407), with CHOL increasing the risk of UTUC-specific mortality (P = 0.0162). Limitations include retrospective design, limited, single-time sampling and relatively small sample size. Conclusions: Lipid profiles were identified as prognostic indicators for UTUC patients post-RNU. It highlights the potential importance of lipid management in improving tumor-related outcomes.

19.
Breast Dis ; 43(1): 19-23, 2024.
Article in English | MEDLINE | ID: mdl-38489166

ABSTRACT

INTRODUCTION: Chemotherapy is conventionally offered to non-stage IV breast cancer patients with metastatic nodes. However, the RxPONDER trial showed that chemotherapy can be omitted in selected patients with 1-3 metastatic nodes if the 21-gene assay recurrence score is ≤25. We aimed to investigate if axillary ultrasound can identify this group of patients with limited nodal burden so that they can undergo upfront surgery followed by gene assay testing, to potentially avoid chemotherapy. METHODS: T1-3, node positive, hormone receptor-positive and HER2-negative breast cancer patients ≥50 years old with axillary lymph node dissection (ALND) were reviewed from 2 centres. Patients with neoadjuvant chemotherapy and bilateral cancers were excluded. Number of ultrasound-detected abnormal axillary nodes, demographic and histological parameters were correlated with the number of metastatic nodes found on ALND. RESULTS: 138 patients were included, 59 (42.8%) and 79 (57.2%) patients had 1-3 and >3 metastatic nodes on ALND respectively. On logistic regression and ROC analysis, the number of ultrasound-detected abnormal nodes was significant (p < 0.001) for predicting limited nodal burden (ROC AUC = 0.7135). Probabilities of <4 metastatic nodes with ultrasound cut-offs of 5, 6 and 8 abnormal nodes were 0.057, 0.026 and 0.005 respectively, with 100% specificity. CONCLUSION: A cut-off of ≤5 ultrasound-detected abnormal nodes can distinguish between patients with limited versus high nodal burden, with high specificity. Hence, incorporating the number of abnormal ultrasound-detected nodes into clinical practice may prove useful in guiding between upfront surgery and gene assay testing or neoadjuvant chemotherapy in this group of patients.


Subject(s)
Breast Neoplasms , Humans , Middle Aged , Female , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Sentinel Lymph Node Biopsy , Lymphatic Metastasis , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymph Node Excision , Genomics , Axilla/pathology , Neoadjuvant Therapy
20.
Cancers (Basel) ; 16(6)2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38539541

ABSTRACT

OBJECTIVE: In a previous study, we proved that an experienced urologist is more likely to adapt to the Hugo RAS system. Based on this, we further examine various parameters in this study. Parameters included in this study consisted of console time, functional outcomes, and oncological outcomes. MATERIALS AND METHODS: A total of 60 patients who underwent robot-assisted radical prostatectomy (RARP) performed by a single surgeon using the da Vinci (DV) system (n = 30) or the Hugo RAS system (n = 30) between March 2023 and August 2023 were included in the analysis. The intraoperative operative time was categorized into vesicourethral anastomosis time and overall console time. Functional and oncological outcomes were documented at the 1st and 3rd postoperative months. Parametric and non-parametric methods were adopted after checking skewness and kurtosis, and an α value of 5% was used to determine the significance. RESULTS: The vesicourethral anastomosis time was significantly lengthened (Hedge's g: 0.87; 95% confidence interval (CI): 0.34-1.39; J factor = 0.987). However, the overall console time was not affected. The functional (postoperative 3rd month: p = 0.130) and oncological outcomes (postoperative 3rd month: p = 0.103) were not significantly different. We also found that the adverse effect on surgical specimens and positive surgical margins was not affected (p = 0.552). CONCLUSION: During the process of adaptation, although intricate motions (such as the vesicourethral anastomosis time) would be lengthened, the overall console time would not change remarkably. In this process, the functional and oncological outcomes would not be compromised. This encourages urologists to adopt the Hugo RAS system in RARP if they have previous experiences of using the DV system, since their trifecta advantage would not be compromised.

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